Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis

Colorectal Cancer Clinical Trial

Official title: An Open-label Phase 1/2 Dose Finding, Safety and Efficacy Study of Oral NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Uncontrolled Brain Metastasis in Patients With Select Solid Tumors.

Status Recruiting

Clinical Trial Summary

This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO212 for the treatment of patients with radiographically-confirmed progression of Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype, and the safety, pharmacokinetics and efficacy of a repeated dose regimen of NEO212 when given with select SOC for the treatment of solid tumor patients with radiographically confirmed uncontrolled brain metastasis. The study will have three phases, Phase 1, Phase 2a and Phase 2b.

Clinical Trial Description

This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO212 for the treatment of patients with radiographically-confirmed progression of Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype, and the safety, pharmacokinetics and efficacy of a repeated dose regimen of NEO212 when given with select SOC for the treatment of solid tumor patients with radiographically confirmed uncontrolled brain metastasis. The study will have three phases, Phase 1, Phase 2a and Phase 2b.

Phase 1 is a standard cohort dose escalation 3+3 design with a modified Fibonacci dose escalation used to determine the maximum tolerated dose to select a recommended Phase 2 dose (RP2D) for Phase 2a and Phase 2b. The initial dose of NEO212 will be 170mg and the dose will increase in successive cohorts (220, 400, 610, 810, and 1,000mg) until a MTD is reached and a RP2D is selected. There will be up to 42 patients enrolled in Phase 1. In the event two DLTs are experienced in any cohort, a dose de-escalation cohort will be followed (with half of the dose increase from the previous cohort) to determine the MTD/RP2D.

Phase 2a is a safety run-in study with a standard 3+3 design used to confirm the safety of the MTD/RP2D of NEO212 when given in combination with select SOC regimens for patients with uncontrolled brain metastasis. There will be up to 12 patients enrolled into each combination regimen to confirm safety. One dose below the NEO212 MTD/RP2D Cohort Dose will be administered as a starting dose to establish safety (3+3), before moving to Phase 2b with the MTD/RP2D (3+3). In the event that two DLTs are experienced for patient receiving the MTD/RP2D in combination with SOC, the dose de-escalation cohort will be expanded to determine the MTD for a newly established Phase 2b Treatment Group.

Phase 2b is a dose expansion study to assess efficacy of NEO212, at the MTD/RP2D in patients with Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype as a single Treatment Group. A second Treatment Group to study the MTD/RP2D of NEO212 in combination with select SOC regimens in patients with solid tumors and uncontrolled brain metastasis established in Phase 2a will be evaluated. Phase 2b will be initiated for patients with Astrocytoma IDH-mutant or Glioblastoma IDH-wildtype alongside Phase 2a. There will be up to 28 patients enrolled to have 27 evaluable patients enrolled in each Phase 2b Treatment Group.

For all phases of the study, NEO212 will be self-administered daily for days 1-5 of a 28-day treatment cycle. ;

Related Conditions & MeSH terms

• Astrocytoma
• Brain Metastases, Adult
• Brain Neoplasms
• Carcinoma
• Carcinoma, Merkel Cell
• Carcinoma, Squamous Cell
• Cervical Cancer
• Colorectal Cancer
• Colorectal Neoplasms
• Diffuse Astrocytoma, IDH-Mutant
• Esophageal Cancer
• Esophageal Squamous Cell Carcinoma
• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• Glioblastoma
• Glioblastoma, IDH-wildtype
• Head and Neck Squamous Cell Carcinoma
• Lung Neoplasms
• Melanoma
• Merkel Cell Carcinoma
• Microsatellite Instability
• Microsatellite Instability-High Solid Malignant Tumor
• Mismatch Repair Deficient Colorectal Cancer
• Neoplasm Metastasis
• Neoplasms
• Non-small Cell Lung Cancer
• Renal Cell Carcinoma
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Urothelial Carcinoma

• NCT number: NCT06047379
• Study type: Interventional
• Source: Neonc Technologies, Inc.
• Contact: Christopher Beardmore
• Phone: 224 218 2408
• Email: chris@anovaevidence.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 1, 2023
• Completion date: August 31, 2026